This book constitutes the refereed proceedings of the 14th Annual International Conference on Research in Computational Molecular Biology, RECOMB 2010, held in Lisbon, Portugal, in April 2010. The 36 revised full papers were carefully reviewed and selected from 176 submissions. The papers cover all areas of computational molecular biology such as molecular sequence analysis; recognition of genes and regulatory elements; molecular evolution; gene expression; biological networks; sequencing and genotyping technologies; genomics; population genetics; systems biology; imaging; computational proteomics; and molecular structural biology.